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AlloHCT From Matched Unrelated Donors in Pts w/ Advanced Hematologic Malignancies & Disorders

Primary Purpose

Leukemia, Lymphoma, Myelodysplastic Syndromes

Status

Active

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

filgrastim

Busulfan

Cyclophosphamide

Cyclosporine

Fludarabine phosphate

Melphalan

Mycophenolate Mofetil

allogeneic hematopoietic stem cell transplantation

umbilical cord blood transplantation

total-body irradiation

Fractionated total body irradiation

About this trial

This is an interventional treatment trial for Leukemia focused on measuring refractory chronic lymphocytic leukemia, adult acute myeloid leukemia in remission, recurrent adult acute myeloid leukemia, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), adult acute lymphoblastic leukemia in remission, accelerated phase chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, recurrent adult Burkitt lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult grade III lymphomatoid granulomatosis, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma, relapsing chronic myelogenous leukemia, recurrent cutaneous T-cell non-Hodgkin lymphoma, secondary acute myeloid leukemia

Eligibility Criteria

0 Years - 120 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS:

Histologically confirmed hematological or lymphatic malignancy, including any of the following:
- Acute myeloid leukemia
  - Relapsed or primary refractory disease with < 10% blasts on peripheral blood smear
  - In first remission with poor risk factors and molecular prognosis [i.e., AML with -5, -7, t(6;9), tri8, -11] (preparative regimen 3 or 4)
- Acute lymphocytic leukemia
  - In second complete remission or higher OR in first remission with poor risk factors, including any of the following (preparative regimen 1 or 2):
    - BCR/ABL by fluorescence in situ hybridization (FISH) or reverse transcriptase-polymerase chain reaction
    - t(9;22)(q34;q11) detected by cytogenetics
    - Chromosomes < 44 by cytogenetics
    - DNA index < 0.81 by flow cytometry
    - Any rearrangement of chromosome 11 that results in disruption of MLL gene (11q23) by cytogenetics and SER
  - In first remission with poor risk factors and molecular prognosis [ALL with Philadelphia chromosome-positive t(9;22), t(4;22), (q34;q11)] (preparative regimen 3 or 4)
- Chronic myelogenous leukemia
  - In accelerated phase or greater (preparative regimen 1 or 2)
  - In accelerated or second chronic phase (preparative regimen 3 or 4)
- Myelodysplastic syndromes
  - With deletion of chromosome 7 or short arm of chromosome 5 (preparative regimen 1 or 2)
  - In high and high-intermediate risk categories (preparative regimen 3 or 4)
- Non-Hodgkin lymphoma in relapse with marrow involvement
- Refractory chronic lymphocytic leukemia
Patients deemed ineligible for conventional high-dose chemotherapy programs (i.e., regimens 1 or 2) due to any of the following concurrent medical conditions may be eligible for regimens 3 or 4 at the discretion of the treating physician and principal investigator (preparative regimen 3 or 4):
- LVEF < 50% and > 40%
- FEV1, FVC, or DLCO < 50%
- Bilirubin > 3 mg/dL
- Creatinine > 2 mg/dL
Two partially HLA-matched umbilical cord blood (UCB) units available
- HLA-matched minimally at 4 of 6 HLA-A, HLA-B, and -DRB1 loci with the patient
  - DRB1 matched by high resolution DNA typing
  - HLA-A and HLA-B matched by low resolution at the "serological match" level
- Two pooled units with a nucleated cell number > 2.5 x 10^7/kg
No available HLA-identical sibling or 1 antigen-mismatched related donor
No available HLA-matched unrelated bone marrow donor

PATIENT CHARACTERISTICS:

See Disease Characteristics
Karnofsky performance status (PS) 60-100% OR Lansky PS 60-100% OR Zubrod PS 0-1
Physiological age 60 or less (at any chronological age)
Weight > 50 kg
Creatinine normal for age OR creatinine clearance by 24-hour urine collection or glomerular filtration rate > 60 mL/min
Bilirubin ≤ 1.5 mg/dL
LVEF ≥ 50%
DLCO ≥ 60% of predicted
No HIV-1 infection
No active uncontrolled infection
Not pregnant
Negative pregnancy test
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Recovered from prior intensive chemotherapy

Sites / Locations

Banner Good Samaritan Medical Center
City of Hope Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Regimen I (FTBI, Cyclophosphamide, Fludarabine)

Regimen II (Busulfan, Fludarabine, Melphalan)

Regimen III (TBI, Cyclophosphamide, Fludarabine)

Regimen IV (Fludarabine, Melphalan)

Arm Description

Patients undergo FTBI 2-3 times a day on days -9 to -6 for a total of 11 fractions. Patients also receive cyclophosphamide IV over 2 hours on days -5 and -4 and fludarabine phosphate IV on days -5 to -2. UCB transplantation: Patients receive 2 combined units of UCB IV on day 0. Patients also receive G-CSF IV or subcutaneously beginning on day 5 (or later) and continuing until blood counts recover. GVHD prophylaxis: Patients receive cyclosporine IV twice daily beginning on day -1 followed by a taper according to institutional guidelines. Patients also receive mycophenolate mofetil orally or IV beginning on day 0 and continuing until day 27 (or as clinically indicated).

Patients receive a test dose of busulfan on day -10 and then dose adjusted busulfan IV 3-4 times daily on days -9 to -6, melphalan IV on days -5 and -4, and fludarabine phosphate IV on days -5 to -2. UCB transplantation: Patients receive 2 combined units of UCB IV on day 0. Patients also receive G-CSF IV or subcutaneously beginning on day 5 (or later) and continuing until blood counts recover. GVHD prophylaxis: Patients receive cyclosporine IV twice daily beginning on day -1 followed by a taper according to institutional guidelines. Patients also receive mycophenolate mofetil orally or IV beginning on day 0 and continuing until day 27 (or as clinically indicated).

Patients receive fludarabine phosphate IV on days -8 to -4 and cyclophosphamide IV over 2 hours on day -3 and undergo TBI (single dose) on day -2. UCB transplantation: Patients receive 2 combined units of UCB IV on day 0. Patients also receive G-CSF IV or subcutaneously beginning on day 5 (or later) and continuing until blood counts recover. GVHD prophylaxis: Patients receive cyclosporine IV twice daily beginning on day -1 followed by a taper according to institutional guidelines. Patients also receive mycophenolate mofetil orally or IV beginning on day 0 and continuing until day 27 (or as clinically indicated).

Patients receive fludarabine phosphate IV on days -7 to -3 and melphalan IV on day -2. UCB transplantation: Patients receive 2 combined units of UCB IV on day 0. Patients also receive G-CSF IV or subcutaneously beginning on day 5 (or later) and continuing until blood counts recover. GVHD prophylaxis: Patients receive cyclosporine IV twice daily beginning on day -1 followed by a taper according to institutional guidelines. Patients also receive mycophenolate mofetil orally or IV beginning on day 0 and continuing until day 27 (or as clinically indicated).

Outcomes

Primary Outcome Measures

Survival Rate at Day 100 After Allogeneic Transplant From Umbilical Cord Blood (UCB)

Number of surviving patients at Day 100 post-transplant divided by number of patients undergone transplantation.

Secondary Outcome Measures

Survival Rate at Day 180 After Allogeneic Transplant From Umbilical Cord Blood (UCB)

Number of surviving patients at Day 180 post-transplant divided by number of patients undergone transplantation.

Full Information

NCT ID

NCT00547196

First Posted

October 19, 2007

Last Updated

March 21, 2023

Sponsor

City of Hope Medical Center

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00547196

Brief Title

AlloHCT From Matched Unrelated Donors in Pts w/ Advanced Hematologic Malignancies & Disorders

Official Title

Allogeneic Stem Cell Transplantation for Patients With Hematological Malignancies Using Multiple Unrelated Cord Blood Units

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

August 16, 2005 (Actual)

Primary Completion Date

November 11, 2009 (Actual)

Study Completion Date

September 9, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

City of Hope Medical Center

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

RATIONALE: Giving chemotherapy with or without total-body irradiation before a donor umbilical cord blood transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil before and after transplant may stop this from happening. PURPOSE: This clinical trial is studying how well four different chemotherapy regimens given with or without total-body irradiation before umbilical cord blood transplant work in treating patients with relapsed or refractory hematologic cancer.

Detailed Description

OBJECTIVES: Primary To determine the survival at day 100 of patients with relapsed, refractory, or poor-risk hematological malignancies treated with four different preparative regimens followed by allogeneic hematopoietic stem cell transplantation (HSCT) using two unrelated umbilical cord blood (UCB) units. Secondary To determine the incidence and timing of neutrophil engraftment in patients treated with these regimens. To determine the incidence and timing of platelet engraftment in patients treated with these regimens. To determine the incidence and severity of acute and chronic graft-versus-host-disease (GVHD) in patients treated with these regimens. To determine the survival at day 180 in patients treated with these regimens. To determine the disease-free survival in patients treated with these regimens. To determine the incidence of primary and secondary engraftment failure in patients treated with these regimens. To determine the incidence of transplantation-related complications (e.g., infection, veno-occlusive disease of the liver, or organ toxicity) in these patients. To determine the incidence of post-transplantation-related lymphoproliferative disease, secondary myelodysplastic syndromes, or other secondary malignancies in these patients. To determine the incidence of relapse in patients treated with these regimens. To determine post-transplantation chimerism in patients treated with these regimens. To determine immune reconstitution in patients treated with these regimens. OUTLINE: This is a multicenter study. Preparative regimens: Patients are assigned to 1 of 4 preparative regimens. Regimen 1 (for patients < 50 years of age and no contraindication to fractionated total-body irradiation (FTBI): Patients undergo FTBI 2-3 times a day on days -9 to -6 for a total of 11 fractions. Patients also receive cyclophosphamide IV over 2 hours on days -5 and -4 and fludarabine phosphate IV on days -5 to -2. Regimen 2 (for patients < 50 years of age and unable to tolerate FTBI due to prior dose-limiting radiotherapy or significant cardiotoxicity): Patients receive a test dose of busulfan on day -10 and then dose adjusted busulfan IV 3-4 times daily on days -9 to -6, melphalan IV on days -5 and -4, and fludarabine phosphate IV on days -5 to -2. Regimen 3* (for patients unable to tolerate regimen 1 or 2; no age exclusion): Patients receive fludarabine phosphate IV on days -8 to -4 and cyclophosphamide IV over 2 hours on day -3 and undergo TBI (single dose) on day -2. Regimen 4* (for patients unable to tolerate regimen 1 or 2): Patients receive fludarabine phosphate IV on days -7 to -3 and melphalan IV on day -2. NOTE: *Treating physician decides the choice between regimen 3 and 4 Umbilical cord blood (UCB) transplantation: Patients receive 2 combined units of UCB IV on day 0. Patients also receive G-CSF IV or subcutaneously beginning on day 5 (or later) and continuing until blood counts recover. Graft-versus-host-disease prophylaxis: Patients receive cyclosporine IV twice daily beginning on day -1 followed by a taper according to institutional guidelines. Patients also receive mycophenolate mofetil orally or IV beginning on day 0 and continuing until day 27 (or as clinically indicated). After completion of study therapy, patients are followed periodically.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Leukemia, Lymphoma, Myelodysplastic Syndromes

Keywords

refractory chronic lymphocytic leukemia, adult acute myeloid leukemia in remission, recurrent adult acute myeloid leukemia, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), adult acute lymphoblastic leukemia in remission, accelerated phase chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, recurrent adult Burkitt lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult grade III lymphomatoid granulomatosis, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma, relapsing chronic myelogenous leukemia, recurrent cutaneous T-cell non-Hodgkin lymphoma, secondary acute myeloid leukemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Regimen I (FTBI, Cyclophosphamide, Fludarabine)

Arm Type

Experimental

Arm Description

Arm Title

Regimen II (Busulfan, Fludarabine, Melphalan)

Arm Type

Experimental

Arm Description

Arm Title

Regimen III (TBI, Cyclophosphamide, Fludarabine)

Arm Type

Experimental

Arm Description

Arm Title

Regimen IV (Fludarabine, Melphalan)

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

filgrastim

Intervention Type

Drug

Intervention Name(s)

Busulfan

Other Intervention Name(s)

Busilvex

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Other Intervention Name(s)

CTX

Intervention Type

Drug

Intervention Name(s)

Cyclosporine

Other Intervention Name(s)

CsA

Intervention Type

Drug

Intervention Name(s)

Fludarabine phosphate

Other Intervention Name(s)

Fludara

Intervention Type

Drug

Intervention Name(s)

Melphalan

Other Intervention Name(s)

Alkeran

Intervention Type

Drug

Intervention Name(s)

Mycophenolate Mofetil

Other Intervention Name(s)

MMF

Intervention Type

Procedure

Intervention Name(s)

allogeneic hematopoietic stem cell transplantation

Other Intervention Name(s)

AlloHCT

Intervention Type

Procedure

Intervention Name(s)

umbilical cord blood transplantation

Intervention Type

Radiation

Intervention Name(s)

total-body irradiation

Other Intervention Name(s)

TBI

Intervention Type

Radiation

Intervention Name(s)

Fractionated total body irradiation

Other Intervention Name(s)

FTBI

Primary Outcome Measure Information:

Title

Survival Rate at Day 100 After Allogeneic Transplant From Umbilical Cord Blood (UCB)

Description

Number of surviving patients at Day 100 post-transplant divided by number of patients undergone transplantation.

Time Frame

From transplant to Day 100 post-transplant

Secondary Outcome Measure Information:

Title

Survival Rate at Day 180 After Allogeneic Transplant From Umbilical Cord Blood (UCB)

Description

Number of surviving patients at Day 180 post-transplant divided by number of patients undergone transplantation.

Time Frame

From transplant up to Day 180 post-transplant

10. Eligibility

Sex

All

Minimum Age & Unit of Time

0 Years

Maximum Age & Unit of Time

120 Years

Accepts Healthy Volunteers

Eligibility Criteria

DISEASE CHARACTERISTICS: Histologically confirmed hematological or lymphatic malignancy, including any of the following: Acute myeloid leukemia Relapsed or primary refractory disease with < 10% blasts on peripheral blood smear In first remission with poor risk factors and molecular prognosis [i.e., AML with -5, -7, t(6;9), tri8, -11] (preparative regimen 3 or 4) Acute lymphocytic leukemia In second complete remission or higher OR in first remission with poor risk factors, including any of the following (preparative regimen 1 or 2): BCR/ABL by fluorescence in situ hybridization (FISH) or reverse transcriptase-polymerase chain reaction t(9;22)(q34;q11) detected by cytogenetics Chromosomes < 44 by cytogenetics DNA index < 0.81 by flow cytometry Any rearrangement of chromosome 11 that results in disruption of MLL gene (11q23) by cytogenetics and SER In first remission with poor risk factors and molecular prognosis [ALL with Philadelphia chromosome-positive t(9;22), t(4;22), (q34;q11)] (preparative regimen 3 or 4) Chronic myelogenous leukemia In accelerated phase or greater (preparative regimen 1 or 2) In accelerated or second chronic phase (preparative regimen 3 or 4) Myelodysplastic syndromes With deletion of chromosome 7 or short arm of chromosome 5 (preparative regimen 1 or 2) In high and high-intermediate risk categories (preparative regimen 3 or 4) Non-Hodgkin lymphoma in relapse with marrow involvement Refractory chronic lymphocytic leukemia Patients deemed ineligible for conventional high-dose chemotherapy programs (i.e., regimens 1 or 2) due to any of the following concurrent medical conditions may be eligible for regimens 3 or 4 at the discretion of the treating physician and principal investigator (preparative regimen 3 or 4): LVEF < 50% and > 40% FEV1, FVC, or DLCO < 50% Bilirubin > 3 mg/dL Creatinine > 2 mg/dL Two partially HLA-matched umbilical cord blood (UCB) units available HLA-matched minimally at 4 of 6 HLA-A, HLA-B, and -DRB1 loci with the patient DRB1 matched by high resolution DNA typing HLA-A and HLA-B matched by low resolution at the "serological match" level Two pooled units with a nucleated cell number > 2.5 x 10^7/kg No available HLA-identical sibling or 1 antigen-mismatched related donor No available HLA-matched unrelated bone marrow donor PATIENT CHARACTERISTICS: See Disease Characteristics Karnofsky performance status (PS) 60-100% OR Lansky PS 60-100% OR Zubrod PS 0-1 Physiological age 60 or less (at any chronological age) Weight > 50 kg Creatinine normal for age OR creatinine clearance by 24-hour urine collection or glomerular filtration rate > 60 mL/min Bilirubin ≤ 1.5 mg/dL LVEF ≥ 50% DLCO ≥ 60% of predicted No HIV-1 infection No active uncontrolled infection Not pregnant Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Recovered from prior intensive chemotherapy

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Anna Pawlowska, MD

Organizational Affiliation

City of Hope Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Banner Good Samaritan Medical Center

City

Phoenix

State/Province

Arizona

ZIP/Postal Code

85006

Country

United States

Facility Name

City of Hope Medical Center

City

Duarte

State/Province

California

ZIP/Postal Code

91010-3000

Country

United States

12. IPD Sharing Statement

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AlloHCT From Matched Unrelated Donors in Pts w/ Advanced Hematologic Malignancies & Disorders

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